The investigators have discovered that a defined extract of Chinese sweet leaf tea (Rubus suavissimus) is anti-angiogenic in a human-tissue based angiogenesis assay and have observed potent tumor growth inhibition of the extract when injected intraperitoneally to a tumor-bearing rat. Preliminary cytotoxicity evaluation found this anti-angiogenic extract was not significantly cytotoxic to human cancer cell lines. Gallic acid has been identified as one of the components that is partially responsible for the extract's antiangiogenic activity. Further testing has revealed a surprising result - the gallic acid-containing extract is 10-fold more potent than pure gallic acid in producing inhibition of angiogenesis, indicative of involvement of other, perhaps more potent inhibitors. Fractionation of this aqueous extract resulted in the complete recovery, in a simple, repeatable, one-step column chromatography method, of all the potent antiangiogenic ingredients into a substantially refined leaf extract, accounting for only 6% (w/w) of the dried leaves. Further subfractionation of this refined extract confirmed the existence of other active anti-angiogenic components. Based on these results the investigators propose to identify these anti-angiogenic compounds and develop a quality control protocol for production of the refined extract, assess relative toxicity in vitro and in vivo, determine the efficacy in stopping tumor growth in mice and rat models (pancreatic carcinoma), and explore mechanisms of action (e.g. anti-VEGF). When these specific aims are accomplished in this R21, the very concept of having a potential orally bioavailable, nontoxic, highly active anti-angiogenic component (proven against growth of HUMAN blood vessels) will be further investigated in an R01 that will further define the mechanisms of action, characterize the defined extract product, and conduct necessary toxicology studies in anticipation of filing an IND. The very concept of having a potential orally bioavailable, nontoxic, highly active anti-angiogenic component (proven against growth of HUMAN blood vessels) is a truly exciting thought. This research, when successfully completed, will set the stage for clinical evaluation of a targeted therapy for cancer using a novel, dietary approach. [unreadable] [unreadable] [unreadable]